Microtubules, serving as a major constituent part of a cytoskeleton, are composed of α-tubulin and β-tubulin heterodimers, have dynamic characteristics of polymerization, and depolymerization, and play important roles in such processes as cell morphology maintenance, cell division, signal transduction, and material transport.
Anti-microtubule drugs have already become a major class of chemotherapy drugs, and are widely applied to clinical treatment of various tumors. Tubulin inhibitors affect and interfere with the dynamics of polymerization and depolymerization of the tubulin by binding with specific sites on the tubulin, thereby blocking the formation of M-stage spindles, and arresting the growth of tumor cells at G2/M stage. At present, clinically applied microtubule inhibitors mainly include tubulin depolymerization inhibiting drugs represented by paclitaxel, and tubulin polymerization inhibiting drugs represented by vinblastines. However, the above-mentioned drugs have such problems as great toxic and side effects, easy resulting of drug tolerance, complex structures, and great synthesis difficulty; it has become a hotspot in current anti-tumor drug research to look for novel, high-effect, and low-toxicity microtubule inhibitors.
Hence, designing and synthesizing novel-structure small-molecule tubulin inhibitors is significant for enhancing the specificity and effectiveness of drugs, reducing toxic and side effects, preventing drug tolerance, and so on.